Department of Mathematics, Virginia Tech, 460 McBryde Hall, Blacksburg, VA 24060, USA.
BMC Immunol. 2013 Aug 6;14:35. doi: 10.1186/1471-2172-14-35.
T-cell receptor diversity correlates with immune competency and is of particular interest in patients undergoing immune reconstitution. Spectratyping generates data about T-cell receptor CDR3 length distribution for each BV gene but is technically complex. Flow cytometry can also be used to generate data about T-cell receptor BV gene usage, but its utility has not been compared to or tested in combination with spectratyping.
Using flow cytometry and spectratype data, we have defined a divergence metric that quantifies the deviation from normal of T-cell receptor repertoire. We have shown that the sample size is a sensitive parameter in the predicted flow divergence values, but not in the spectratype divergence values. We have derived two ways to correct for the measurement bias using mathematical and statistical approaches and have predicted a lower bound in the number of lymphocytes needed when using the divergence as a substitute for diversity.
Using both flow cytometry and spectratyping of T-cells, we have defined the divergence measure as an indirect measure of T-cell receptor diversity. We have shown the dependence of the divergence measure on the sample size before it can be used to make predictions regarding the diversity of the T-cell receptor repertoire.
T 细胞受体多样性与免疫能力相关，在进行免疫重建的患者中特别有趣。谱型分析可生成有关每个 BV 基因的 T 细胞受体 CDR3 长度分布的数据，但技术复杂。流式细胞术也可用于生成有关 T 细胞受体 BV 基因使用的数据，但尚未将其与谱型分析进行比较或联合测试。
我们使用流式细胞术和谱型数据定义了一个发散度度量标准，该标准可量化 T 细胞受体库的偏离正常情况。我们表明，在预测的流式细胞术发散度值中，样本量是一个敏感参数，但在谱型发散度值中不是。我们通过数学和统计方法推导了两种校正测量偏差的方法，并预测了当使用发散度作为多样性的替代指标时所需的淋巴细胞数量的下限。
我们使用 T 细胞的流式细胞术和谱型分析，将发散度测量定义为 T 细胞受体多样性的间接测量方法。我们表明，在使用发散度进行预测之前，它对样本量有依赖性，然后才能用于预测 T 细胞受体库的多样性。
